Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection

• Published in: BMC medicine 2022-01, Vol.20 (1), p.26-26, Article 26
• Main Authors: Ryan, Feargal J, Hope, Christopher M, Masavuli, Makutiro G, Lynn, Miriam A, Mekonnen, Zelalem A, Yeow, Arthur Eng Lip, Garcia-Valtanen, Pablo, Al-Delfi, Zahraa, Gummow, Jason, Ferguson, Catherine, O'Connor, Stephanie, Reddi, Benjamin A J, Hissaria, Pravin, Shaw, David, Kok-Lim, Chuan, Gleadle, Jonathan M, Beard, Michael R, Barry, Simon C, Grubor-Bauk, Branka, Lynn, David J
• Format: Article
• Language: English
• Subjects: Analysis; Antibodies, Viral; Antibody responses; Asymptomatic; Chronic illnesses; Complications; Coronaviruses; COVID-19; COVID-19 - complications; CXCR3 protein; Disease; Gene expression; Gene sequencing; Humans; Immune response; Immune System; Immunity; Immunoglobulin G; Immunoregulation; Infections; Leukocytes (neutrophilic); Long-term effects; Lymphocytes; Lymphocytes T; Medical research; Monocytes; Pandemics; Perturbation; Proteins; Recovery (Medical); Respiratory diseases; RNA sequencing; RNA-Seq; SARS-CoV-2; Serology; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Signs and symptoms; T cell; Transcription; Transcriptomes; Viral diseases; Viruses
• ISSN: 1741-7015; 1741-7015
• DOI: 10.1186/s12916-021-02228-6

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious respiratory virus which is responsible for the coronavirus disease 2019 (COVID-19) pandemic. It is increasingly clear that recovered individuals, even those who had mild COVID-19, can suffer from persistent symptoms for many months after infection, a condition referred to as "long COVID", post-acute sequelae of COVID-19 (PASC), post-acute COVID-19 syndrome, or post COVID-19 condition. However, despite the plethora of research on COVID-19, relatively little is known about the molecular underpinnings of these long-term effects. We have undertaken an integrated analysis of immune responses in blood at a transcriptional, cellular, and serological level at 12, 16, and 24 weeks post-infection (wpi) in 69 patients recovering from mild, moderate, severe, or critical COVID-19 in comparison to healthy uninfected controls. Twenty-one of these patients were referred to a long COVID clinic and > 50% reported ongoing symptoms more than 6 months post-infection. Anti-Spike and anti-RBD IgG responses were largely stable up to 24 wpi and correlated with disease severity. Deep immunophenotyping revealed significant differences in multiple innate (NK cells, LD neutrophils, CXCR3+ monocytes) and adaptive immune populations (T helper, T follicular helper, and regulatory T cells) in convalescent individuals compared to healthy controls, which were most strongly evident at 12 and 16 wpi. RNA sequencing revealed significant perturbations to gene expression in COVID-19 convalescents until at least 6 months post-infection. We also uncovered significant differences in the transcriptome at 24 wpi of convalescents who were referred to a long COVID clinic compared to those who were not. Variation in the rate of recovery from infection at a cellular and transcriptional level may explain the persistence of symptoms associated with long COVID in some individuals.